OVERALL DESCRIPTION (Taken from the application) The University of Southern California Research Center for Liver Diseases, funded since 1995, has the goal of fostering and facilitating inter-disciplinary research in liver and digestive diseases. The center has 34 members and 13 affiliated members. The Biomedical Research Base consists of four major themes supported by 45 peer-reviewed grants totaling $6.5 million in annual direct costs. These themes include: a) viral hepatitis and liver cancer; b) liver injury: hepatotoxicity, inflammation, fibrosis; c) cell biology and transport; and d) metabolism, signal transduction and gene expression. Four core facilities support this research base: 1) Administrative Core which oversees the operations and budget of the center; the Center Director, Associate Director, Administrator and External Advisory Board oversee the utilization of the cores, the pilot/feasibility program, the Named New Investigator Award, and the enrichment program (seminar series and annual symposium); a Mathematical Analysis Modeling Subcore is available to center members through the Administrative Core; 2) Molecular Biology Core, composed of three major activities (supporting research in gene expression, techniques and equipment) and a Viral Vector Subcore to enhance gene delivery research; 3) Cell Biology Core divided into a Subcellular Organelle Core which provides membrane fractionation, highly enriched sinusoidal and canalicular plasma membrane vesicles, mitochondria and isolated perfused liver, and a Confocal Microscope Subcore for imaging of live and fixed cells; 4) Cell Culture Core divided into Parenchymal Subcore which provides isolated and primary cultured rat, mouse and human hepatocytes and various cell lines, and a Nonparenchymal Subcore which provides isolated and cultured Kupffer cells, hepatic stellate cells and sinusoidal endothelial cells. The center supports Pilot and Feasibility projects in diverse areas related to the themes of the Research Base. Current projects supported by the center include targeting gene therapy to the liver, abnormal liver development in retinoic acid receptor defective mice, the identification and characterization of nitric oxide synthase in liver mitochondria, and the identification of mutations in the epoxide hydrolase gene in human subjects with impaired hepatic uptake of bile acids. The USC Research Center for Liver Diseases is dedicated to attracting and promoting research aimed at understanding, preventing, and treating liver and digestive diseases.